Success Rate of Swept-Source Optical Coherence Tomography Biometry of Eyes of Elementary School Students.

Purpose: To determine the success rate of swept-source optical coherence tomography (SS-OCT) biometry (OA-2000) in elementary school students. Methods: This was a prospective observational longitudinal study of 115 right eyes of elementary school students who were 8- to 9-years-old at the initial examination. Biometric measurements of the eyes were performed annually for three years, viz., during the third, fourth, and fifth grades. The success rates of obtaining data from optical biometric measurements of the axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), pupillary diameter (PD), corneal diameter (CD), and corneal curvature (CC) were determined. Results: The AL, CCT, and CC could be measured in all images at the three measurement times in all subjects. The success rate of the measurements of the ACD was 92.2% in the third grade and 100% in the fourth and fifth grade. The LT was successfully measured in 88.7% in the third grade, 99.1% in the fourth grade, and 100% in the fifth grade. The PD was successfully measured in 100% of the third grade, 96.0% of the fourth grade, and 100% in the fifth grade. The CD was successfully measured in 84.3% in the third grade, 66% in the fourth grade, and 100% in the fifth grade. Conclusion: SS-OCT can obtain accurate measures of all ocular parameters in the primary school students with high success rates. However, care should be taken especially in analyzing the ACD, LT, PD, and CD because errors can occur in some cases.

Artificial intelligence for classifying uncertain images by humans in determining choroidal vascular running pattern and comparisons with automated classification between artificial intelligence.

PURPOSE: Abnormalities of the running pattern of choroidal vessel have been reported in eyes with pachychoroid diseases. However, it is difficult for clinicians to judge the running pattern with high reproducibility. Thus, the purpose of this study was to compare the degree of concordance of the running pattern of the choroidal vessels between that determined by artificial intelligence (AI) to that determined by experienced clinicians. METHODS: The running pattern of the choroidal vessels in en face images of Haller's layer of 413 normal and pachychoroid diseased eyes was classified as symmetrical or asymmetrical by human raters and by three supervised machine learning models; the support vector machine (SVM), Xception, and random forest models. The data from the human raters were used as the supervised data. The accuracy rates of the human raters and the certainty of AI's answers were compared using confidence scores (CSs). RESULTS: The choroidal vascular running pattern could be determined by each AI model with an area under the curve better than 0.94. The random forest method was able to discriminate with the highest accuracy among the three AIs. In the CS analyses, the percentage of certainty was highest (66.4%) and that of uncertainty was lowest (6.1%) in the agreement group. On the other hand, the rate of uncertainty was highest (27.3%) in the disagreement group. CONCLUSION: AI algorithm can automatically classify with ambiguous criteria the presence or absence of a symmetrical blood vessel running pattern of the choroid. The classification was as good as that of supervised humans in accuracy and reproducibility.

Recent Advances and Clinical Application of Color Scanning Laser Ophthalmoscope.

Scanning laser ophthalmoscopes (SLOs) have been available since the early 1990s, but they were not commonly used because their advantages were not enough to replace conventional color fundus photography. In recent years, color SLOs have improved significantly, and the colored SLO images are obtained by combining multiple SLO images taken by lasers of different wavelengths. A combination of these images of different lasers can create an image that is close to that of the real ocular fundus. One advantage of the advanced SLOs is that they can obtain images with a wider view of the ocular fundus while maintaining a high resolution even through non-dilated eyes. The current SLOs are superior to the conventional fundus photography in their ability to image abnormal alterations of the retina and choroid. Thus, the purpose of this review was to present the characteristics of the current color SLOs and to show how that can help in the diagnosis and the following of changes after treatments. To accomplish these goals, we will present our findings in patients with different types of retinochoroidal disorders.

QUANTIFICATION OF VESSELS OF HALLER'S LAYER BASED ON EN-FACE OPTICAL COHERENCE TOMOGRAPHY IMAGES.

PURPOSE: To quantify the vessels of Haller's layer of normal subjects in en-face optical coherence tomographic images. METHODS: One hundred and seventy-two normal eyes were studied. En-face images of the top 25% slab of Haller's layer was analyzed. The vessel area, vessel length, and mean vessel diameter were calculated. The vessel running pattern was quantified for the degree of symmetry and designated as the "symmetry index." The coefficient of correlation between each choroidal parameter and the age, sex, axial length, and central choroidal thickness was determined. RESULTS: The vessel area was 23.4 ± 3.6 mm2, vessel length was 164.6 ± 24.1 mm, mean vessel diameter was 0.143 ± 0.019 mm, and the symmetry index was 58.6 ± 6.1%. Multiple regression analysis showed that the vessel area was significantly correlated with the age (R = -0.421, P < 0.001) and central choroidal thickness (R = 0.315, P < 0.001). The vessel length was significantly correlated with the age (R = -0.391, P = 0.024) and central choroidal thickness (R = -0.410, P < 0.001). The mean vessel diameter was significantly correlated with the age (R = -0.107, P = 0.024) and central choroidal thickness (R = 0.775, P < 0.001). The correlation between the symmetry index and any clinical findings was not significant. CONCLUSION: Quantification of en-face images of Haller's layer provide new biomarkers of the choroid.

Running pattern of choroidal vessel in en face OCT images determined by machine learning-based quantitative method.

PURPOSE: To evaluate the new method to quantitate the running pattern of the vessels in Haller's layer in en face optical coherence tomographic (OCT) images using the new algorithm. METHODS: A retrospective and cross-sectional study. The en face image of top 25% slab of Haller's layer was analyzed. The vascular area in these images was calculated after binarization. Then, the vessels were thinned, and the total length of the vessels and the mean vessel diameter were calculated. Based on the angle of vessel running, "natural oblique vessel" was defined. The ratio of the natural oblique vessel to the whole vessels was defined as the "symmetry index". To examine the reproducibility of the software, the images obtained on two different examination dates of the same subject (25 eyes of 25 healthy subjects) were analyzed. Also, to compare the symmetry index and subjective evaluations, 180 eyes and 180 healthy subjects were analyzed. The subjective evaluations classified the images into 3 groups, the Symmetrical, Semi-symmetrical, and Asymmetrical types. Symmetry index was compared in each group. RESULTS: The inter-measurement correlation coefficient (ICC) of the vessel area, vessel length, and vessel diameter were 0.955, 0.934, and 0.954, respectively. The ICC of the symmetry index was 0.926. The symmetry index of the Symmetrical type was 60.4 ± 7.2%, that of the Semi-symmetry type was 56.2 ± 4.6%, and that of the Asymmetry type was 52.6 ± 5.2%. CONCLUSIONS: The present algorithm can analyze vessels in Haller's layer of the en face images of choroid in an objective manner with good repeatability.

Regional Differences of Choroidal Structure Determined by Wide-Field Optical Coherence Tomography.

Purpose: To compare the submacular to the perimacular choroidal structure in images obtained by wide-field optical coherence tomography (OCT). Methods: Thirty eyes of 30 healthy volunteers (15 men) were studied. Twelve wide-field radial circumferential scans were recorded with enhanced depth imaging OCT from the macular and perimacular zones. The sizes of the luminal and stromal areas of the choroid were determined. The two zones were subdivided into the superior, inferior, nasal, and temporal sectors. The total choroidal area, the luminal and stromal areas, and the luminal ratio of each sector were compared. Results: All of the choroidal structural parameters analyzed in the present study were largest in the superior sector followed by the temporal, inferior, and nasal sectors. The coefficients of variation were larger in the perimacular zone than in the macular zone: The luminal ratio in the macular zone varied by 1.2%, and that in perimacular zone varied by 4.2%. Conclusions: The variations in the ratios of the luminal areas of the choroid in the wide-field OCT images are slight in the macular zone but considerable in the perimacular zone.

Kago-Eye2 software for semi-automated segmentation of subfoveal choroid of optical coherence tomographic images.

PURPOSE: To determine the capabilities of the "Kago-Eye2" software to semi-automatically segment the choroid in the optical coherence tomographic (OCT) images. STUDY DESIGN: A cross-sectional, prospective study of 44 healthy volunteers. METHODS: The Kago-eye2 software was developed to detect the border between Choriocapillaris and Sattler's layer (C-S) and between Sattler's layer and Haller's layer (S-H). The intra- and inter-grader agreements were determined for the segmentations made with semi-automated and manual analysis using the Kago-Eye2 software. The inter-method agreements were determined for two independent graders. RESULTS: Forty-four right eyes of 44 heathy volunteers (22 men) with a mean age of 35.0 ± 8.8 years were studied. The intra-grader agreement of the C-S border was 0.97 for grader 1 and 0.892 for grader 2 for the manual segmentation, and 0.908 for grader 1 and 0.842 for grader 2 for the Kago-Eye2 segmentation. For the S-H border, the intra-grader agreement was 0.96 for grader 1 and 0.981 for grader 2 for manual segmentation and 0.855 for grader 1 and 0.839 for grader 2 with the Kago-Eye2. For the C-S and S-H border, the inter-grader agreement was 0.548 and 0.902 for manual segmentation and 0.947 and 0.833 for the Kago-Eye2. The inter-method agreement was 0.565 for the C-S border and 0.759 for the S-H border. CONCLUSION: The Kago-Eye2 software can segment the layers of the subfoveal choroid with good reproducibility and repeatability. We conclude that the Kago-Eye2 software can be used for semi-automatic segmentation of the choroidal layers.

Automated segmentation of en face choroidal images obtained by optical coherent tomography by machine learning.

PURPOSE: To develop an automated method to segment the choroidal layers of en face optical coherent tomography (OCT) images by machine learning. STUDY DESIGN: A cross-sectional, prospective study of 276 eyes of 181 healthy subjects. METHODS: OCT en face images of the choroid were obtained every 2.6 µm from the retinal pigment epithelium (RPE) to the chorioscleral border. The images at the start of the choriocapillaris, start of Sattler's layer, and start of Haller's layer were identified, and the image numbers from the RPE line were taken as the teacher data. Forty-one feature quantities of each image were extracted. A support vector machine (SVM) model was created from each feature value of the training data, and a coefficient of determination was calculated for each layer of the choroid by a fivefold cross validation. Next, the same evaluation was performed after creating a SVM model with selected effective feature quantities. RESULTS: The mean coefficient of determination using all features was 0.9853 ± 0.0012. Nine effective feature quantities (relative choroid thickness, mean/kurtosis/variance of brightness, FFT_ skewness, k0_vessel width, k1/k2/k4_vessel area) were selected, and the mean of the coefficient of determinations with these quantities In this model was 0.9865 ± 0.0001. The number of errors in the image number at the start of each layer was 1.01 ± 0.79 for the choriocapillaris, 1.13 ± 1.12 for Sattler's layer, and 3.77 ± 2.90 for Haller's layer. CONCLUSION: Automated stratification of the choroid in en face images can be done with high accuracy through machine learning.

Objective evaluation of size and shape of superficial foveal avascular zone in normal subjects by optical coherence tomography angiography.

This study was conducted to investigate the size and shape of the foveal avascular zone (FAZ) determined by optical coherence tomography angiography (OCTA) and the relationship of the size and shape to the clinical findings in normal subjects. This was a cross-sectional study with seventy eyes of 70 volunteers. The size of the superficial FAZs were assessed by its area, length of perimeter, and Feret's diameter, and the shape by the circularity, axial ratio, roundness, and solidity. The correlations between each parameter and the clinical findings were statistically determined. The coefficients of variation (CV) of the parameters of FAZ size were higher than that of the parameters of FAZ shape. The refractive error and axial length were significantly correlated with area-related factors. The central macular thickness (CMT) was significantly correlated with all parameters. Although the CMT was a critical factor that was significantly correlated with the size and shape characteristics of the FAZ, the shape might be a better factor for characterizing the FAZ than the size because of the low CV of shape-related factors and the characteristics are less affected by the other ocular factors.

Semi-automated software to measure luminal and stromal areas of choroid in optical coherence tomographic images.

PURPOSE: To determine the capabilities of "EyeGround" software in measuring the choroidal cross sectional areas in optical coherence tomographic (OCT) images. STUDY DESIGN: Cross sectional, prospective study. METHODS: The cross-sectional area of the subfoveal choroid within a 1500 µm diameter circle centered on the fovea was measured both with and without using the EyeGround software in the OCT images. The differences between the evaluation times and the results of the measurements were compared. The inter-rater, intra-rater, inter-method agreements were determined. RESULTS: Fifty-one eyes of 51 healthy subjects were studied: 24 men and 27 women with an average age of 35.0 ± 8.8 years. The time for analyzing a single image was significantly shorter with the software at 3.2±1.1 min than without the software at 12.1±5.1 min (P <0.001). The inter-method correlation efficient for the measurements of the whole choroid was high [0.989, 95% CI (0.981-0.994)]. With the software, the inter-rater correlation efficient was significantly high [0.997, 95% CI (0.995-0.999)], and the intra-rater correlation efficient was also significantly high [0.999, 95% CI (0.999-1.0)]. CONCLUSION: The EyeGround software can measure the choroidal area in the OCT cross sectional images with good reproducibility and in a significantly shorter times. It can be a valuable tool for analyzing the choroid.

Luminal and stromal areas of choroid determined by binarization method of optical coherence tomographic images.

PURPOSE: To determine the proportion of luminal and stromal areas of normal choroids in the optical coherence tomographic (OCT) images obtained by enhanced depth imaging (EDI)-OCT. DESIGN: A prospective, masked, observational cross-sectional study. METHODS: setting: This study was performed at the Kagoshima University Hospital, Japan. STUDY POPULATION: One hundred and eighty right eyes of 180 healthy volunteers (106 women; mean age of 55.9 years) without ocular pathology. observational procedures: The EDI-OCT images of the posterior choroid 7500 µm from the optic disc in the horizontal plane were converted to binary images. The total cross-sectional choroidal area, luminal area, and stromal area of the choroid were measured. MAIN OUTCOME MEASURES: Correlations between clinical factors and each choroidal structure and ratio of luminal/stromal areas were determined. The correlations of each choroidal structure and the age, sex, axial length (AL), and refractive errors were calculated. RESULTS: The mean total cross-sectional choroidal area was 1.84 mm(2) (luminal area 1.21 mm(2) and stromal area 0.63 mm(2)). Multivariate analysis (standardized partial regression coefficient) showed that age (-0.723, P < .001) was significantly correlated with the reduced area of the choroid, and the correlation was greater than that for the AL (-0.408, P < .001). The ratio of luminal/stromal area was significantly reduced in eyes with longer ALs (-0.531, P < .001), and the strength of the correlation was greater than that of age (-0.389, P < .001). CONCLUSIONS: Although both the luminal and the stromal areas decrease with increasing age and with longer ALs, the degree of decrease and areas affected were not the same.

Choroidal structure in normal eyes and after photodynamic therapy determined by binarization of optical coherence tomographic images.

PURPOSE: To determine changes in choroidal structure by binarization of optical coherence tomographic (OCT) images. METHODS: Choroidal images were recorded by enhanced depth imaging OCT. The subfoveal choroidal images were analyzed, and the luminal and interstitial areas were converted to binary images by the Niblack method. The interrater, intrarater, and intersession agreements of the binary images were determined for healthy eyes. In eyes with age-related macular degeneration (AMD), the binary images of the choroid before photodynamic therapy (PDT) were compared to those after PDT. The untreated fellow eyes were studied as controls. RESULTS: In healthy eyes, the average ratio of the luminal to choroidal area was 65.4%. The interrater agreement rate was high, with intraclass correlation coefficient (ICC) 0.985 and 0.988 for the choroid and luminal areas, respectively. The intrarater ICC was 0.996 for the choroid and 0.997 for the luminal areas. The intersession ICC was 0.993 for the choroid and 0.984 for the luminal areas. In eyes with AMD, the subfoveal choroidal area, the luminal area, and the interstitial areas were thinner 6 months after PDT (all P < 0.01, Wilcoxon signed-rank sum test). The ratio of the luminal to choroidal area was significantly decreased to 62.8% (P < 0.01, Wilcoxon signed-rank sum test). The ratio for the fellow eyes was not significantly changed. CONCLUSIONS: The Niblack binarization method can be used to analyze the luminal area of choroid in an OCT image with good repeatability and reproducibility. The change in the subfoveal choroidal area after PDT is due mainly to a decrease in the luminal areas.

Comparisons of choroidal thickness of normal eyes obtained by two different spectral-domain OCT instruments and one swept-source OCT instrument.

PURPOSE: We compared the subfoveal choroidal thickness (SFCT) measured on the images obtained by two spectral-domain optical coherence tomographic (SD-OCT) instruments and one swept-source OCT (SS-OCT) instrument. METHODS: A cross-sectional, prospective noninterventional study was done in which SFCT was measured in the images obtained by two SD-OCT instruments; Heidelberg Spectralis-OCT (Spectralis-SD-OCT) and Topcon 3D OCT-1000 Mark II (Topcon-SD-OCT). Images also were obtained with SS-OCT Atlantis DRI OCT-1 (DRI-SS-OCT). After manual segmentation, the measurements were made using the calipers embedded in each instrument. The intrarater, interrater, and intermachine agreements were assessed. RESULTS: We studied 35 subjects. The intrarater correlation coefficient (95% confidence interval) was 0.994 (0.988-0.994) for Spectralis-SD-OCT, 0.996 (0.993-0.998) for Topcon-SD-OCT, and 0.997 (0.991-0.998) for DRI-SS-OCT (P < 0.001). The interrater correlation coefficient was 0.995 (0.991-0.998) for Spectralis-SD-OCT, 0.995 (0.990-0.998) for Topcon-SD-OCT, and 0.996 (0.992-0.998) for DRI-SS-OCT (P < 0.001). The average SFCT was 273.2 µm with Spectralis-SD-OCT, 269.1 µm with the Topcon-SD-OCT, and 280.5 µm with DRI-SS-OCT. The intermachine correlation coefficient was 0.982 (0.964-0.991) for Spectralis-SD-OCT versus Topcon-SD-OCT, 0.907 (0.815-0.953) for Topcon-SD-OCT versus DRI-SS-OCT, and 0.911 (0.832-0.954) for DRI-SS-OCT versus Spectralis-SD-OCT (P < 0.001). The SFCT measured with DRI-SS-OCT was significantly thicker than that with Topcon-SD-OCT, with a mean difference of 11.41 ± 30.27 µm (P = 0.032). CONCLUSIONS: In normal adult eyes, there was good reproducibility and repeatability of SFCT measurements obtained by the SD-OCT and SS-OCT instruments. However, the choroid measured with DRI-SS-OCT was thicker than that measured with both SD-OCT instruments, and, thus, the choroidal thickness should not be compared between the SD-OCT and SS-OCT instruments. (www.umin.ac.jp/ctr number, UMIN000011259.).

Fulminant type 1 diabetes mellitus acutely emerged during pregnancy.

A pregnant woman at 32 weeks of gestation was emergently admitted to our hospital with symptoms of nausea, vomiting, and uterine contraction. Cardiotocogram demonstrated a loss of variability and late deceleration in fetal heart rate pattern. Emergency cesarean section was performed, and a male infant weighing 1750 g was born with Apgar scores of 1 at 1 min, and 3 at 5 min after delivery. After cesarean section, the patient developed an acetone breath odor, and blood examination demonstrated remarkable acidemia and an extremely high level of blood glucose. The patient was diagnosed with ketoacidosis with acute onset of fulminant type 1 diabetes mellitus. Intensive care was applied due to the severe diabetes mellitus conditions. The patient's general condition ameliorated during the postoperative period, although there was a possibility of neurological complications in the infant.

Effect of haemodialysis on the pharmacokinetics of antineoplastic drugs.

Since renal failure itself creates an immunocompromised situation, malignant tumours in haemodialysis patients are increasing due to the prolonged lifespan of these patients. In treating these patients with anticancer agents, dosage reduction is often recommended to avoid adverse drug reactions, particularly for drugs with extensive renal excretion. On the other hand, if an anticancer drug is removed significantly by haemodialysis, dosage increase would be required to ensure adequate therapeutic efficacy. We address in this review the clinical pharmacokinetic aspects of antineoplastic therapy, and the application of pharmacokinetic principles to the adjustment of dosage of anticancer agents in haemodialysis patients.

Association of vitamin D and estrogen receptor gene polymorphism with the effects of longterm hormone replacement therapy on bone mineral density.

We longitudinally studied whether vitamin D receptor (VDR) and estrogen receptor (ER) gene polymorphisms in Japanese women influenced the effect of longterm hormone replacement therapy (HRT) on bone mineral density (BMD) in the lumbar spine. The 81 subjects were aged 40 to 64 years (mean +/- SEM, 49.5 +/- 0.6 years), and had received sequential or continuous HRT regimens, including 0.625 mg of conjugated equine estrogen and 2.5 to 5 mg of medroxy-progesterone acetate, for at least 3 years. Genomic DNA was extracted from blood cells, and analyzed for restriction fragment length polymorphism, using the restriction endonucleases Taq I, Apa I, and Fok I for VDR, and Pvu II and Xba I for ER. At 1 year, subjects with a Taq I genotype of TT (i.e., site absent) showed a significantly greater increase in BMD with treatment (DeltaBMD) than subjects with the Tt genotype (2.6 +/- 0.5% vs -0.8 +/- 1.4%; P = 0.016). A small difference between genotypes remained at 2 years (3.8 +/- 0.6% vs 0.8 +/- 1.6%; P = 0.069), but no significant difference between genotypes was seen at 3 years. In multiple regression analyses, DeltaBMD at 1 year was significantly affected by VDR- Taq I, Apa I, and ER- Pvu II genotypes and by age at treatment initiation, although at 3 years or more, DeltaBMD was significantly affected only by age. These results indicate that Taq I VDR gene polymorphism predicted the effect on lumbar BMD for the first year of HRT in Japanese women, and that the differences in BMD versus the polymorphism disappeared if the treatment was continued for over 2 years.

Effect of vitamin D receptor and estrogen receptor gene polymorphism on the relationship between dietary calcium and bone mineral density in Japanese women.

In a longitudinal analysis of the results of bone mineral density (BMD) screenings conducted in local communities, we examined the effect of lifestyle improvements on BMD and investigated the influence of allelic variations of the vitamin D receptor ( VDR) and estrogen receptor ( ER) genes. The subjects were 484 women (age, 24-80 years) who underwent BMD screenings at least twice between 1994 and 2002. We conducted BMD measurements of the lumbar spine by dual-energy X-ray absorptiometry and performed a simple questionnaire survey of lifestyle factors. Women receiving pharmacotherapy, or those with bone fractures, were excluded, leaving 338 women eligible for the study. They were retrospectively divided into three groups: (i) premenopause, women who were at least 5 years preceding menopause; (ii) perimenopause, women who were within 5 years before or after menopause; and (iii) postmenopause, women who were at least 5 years past menopause. There was no correlation at all between improvements of lifestyle factors (i.e., calcium intake from dairy products and time spent walking) and fluctuations in lumbar-spine BMD after 1, 3, or 5 years in the pre-, peri-, and postmenopausal groups. For women in the postmenopausal group, the PP genotype for the ER gene correlated with a significantly higher initial BMD than those with the Pp and pp genotypes ( P = 0.04). After 3 years, presence of the TT genotype of Taq I of VDR gene polymorphism exhibited positive correlations ( r = 0.29, P = 0.03) with the improvements in calcium intake and in lumbar spine BMD for the perimenopausal group, whereas the Tt genotype showed negative correlations ( r = -0.48, P = 0.04). After 1, 3, and 5 years, presence of the Tt genotype showed a tendency toward a negative correlation with the increases in calcium intake and in lumbar spine BMD for the pre- and perimenopausal groups, although almost of these were not significantly different. In this study, we could not prove a positive correlation between the improvement of lifestyle and the fluctuation of BMD within a 5-year timeframe, although the polymorphisms within the VDR gene may have some influence.